1
Supplementary information
Calculation of NTHi frequency on Invasive Disease Based on data from the paper by Gabastou et al. [1]: • 2,782 Haemophilus influenzae strains were analyzed
• 24.7% of all H. influenzae strains collected during 2000-2005 were non-typeable H. influenzae (NTHi)
• The percentage of NTHi increased with time (Figure 1A of [1]); therefore, in 2007, it is estimated that 38% of all H. influenzae strains were NTHi (Figure).
• The estimated number of NTHi strains identified in 2007 was therefore 0.38 × 2,782 = 1,057 • 1,573 H. influenzae strains were from meningitis (estimated NTHi = 0.38 × 1,573 = 598) and 602
H. influenzae strains were from sepsis/bacteremia (estimated NTHi = 0.38 × 602 = 229) (from Table 6 of [1])
• 6,753 cases of meningitis were due to S. pneumoniae (from Table 2 of [1]) and 3,783 cases of sepsis/bacteremia were due to S. pneumoniae (from Table 2 of [1])
• Therefore the ratio of S. pneumoniae to NTHi meningitis was assumed to be 11:1 and S. pneumoniae to NTHi bacteremia, 17:1.
2 Supplementary Table 1 Pneumococcal meningitis epidemiology by age group
Age group Annual incidence (per 100,000 inhabitants)a
Fatality (%)b Cases with
neurological sequelae (%)b Cases with hypoacusia (%)b <1 year 5.1 20.0 19.4 3.4 1 year 1.4 10.0 19.4 3.4 2 years 1.4 10.0 19.4 3.4 3 years 1.9 5.0 19.4 3.4 4 years 1.9 5.0 19.4 3.4 5-9 years 4.9 2.0 19.4 3.4 10-14 years 1.0 2.0 19.4 3.4 15-19 years 4.8 2.0 18.2 4.4 20-24 years 1.8 9.3 18.2 4.4 25-29 years 1.2 9.3 18.2 4.4 30-34 years 1.1 9.3 18.2 4.4 35-39 years 2.4 9.3 18.2 4.4 40-44 years 2.4 9.3 18.2 4.4 45-49 years 2.8 12.5 18.2 4.4 50-54 years 3.8 12.5 18.2 4.4 55-59 years 3.0 12.5 18.2 4.4 60-64 years 3.0 12.5 18.2 4.4 65-69 years 2.5 25.0 18.2 4.4 70-74 years 1.9 25.0 18.2 4.4 75-79 years 2.5 25.0 18.2 4.4 80-84 years 6.7 25.0 18.2 4.4 85-89 years 6.7 25.0 18.2 4.4 ≥ 90 years 6.7 25.0 18.2 4.4 a
Based on mortality from Oficina General de Estadística e Informática (OGEI) 2006 [2]divided by the hospital fatality. The percentage of cases attributable to pneumococcus were based on Delphi panel
3 results from Peru (for pediatric patients) or average of Delphi panels from Chile, Brazil, Mexico and Colombia (for adults).
b
Based on Delphi panel results from Peru (for pediatric ages) or average of Delphi panels results from Chile, Brazil, Mexico and Colombia (for adults).
4 Supplementary Table 2 Epidemiology of pneumococcal bacteremia by age group
Age group Annual incidence (per
100,000 inhabitants)a Fatality (%)b <1 year 54.2 20.0 1 year 9.7 15.0 2 years 9.7 15.0 3 years 7.3 10.0 4 years 7.3 10.0 5-9 years 2.5 2.0 10-14 years 2.5 2.0 15-19 years 2.5 2.0 20-24 years 4.5 11.9 25-29 years 4.0 11.9 30-34 years 4.8 11.9 35-39 years 5.5 11.9 40-44 years 9.2 11.9 45-49 years 8.6 17.5 50-54 years 12.8 17.5 55-59 years 19.8 17.5 60-64 years 33.0 17.5 65-69 years 54.7 28.8 70-74 years 86.1 28.8 75-79 years 144.8 28.8 80-84 years 475.3 28.8 85-89 years 475.3 28.8 ≥90 years 475.3 28.8 a
Based on mortality from Oficina General de Estadística e Informática (OGEI) 2006 [2] divided by the hospital fatality. The percentage of cases attributable to pneumococcus was based on Peru Delphi panel results (for the pediatrics ages) or average of Delphi panels results from Chile, Brazil, Mexico and Colombia (for adults).
5 b
Based on the Peru Delphi results (for the pediatrics ages) or average of Delphi panels results from Chile, Brazil, Mexico and Colombia (for adults).
6 Supplementary Table 3 Pneumonia epidemiology from all causes by age group
Age group Annual hospitalization rate (per 100,000 inhabitants)a
Fatality (%)b Annual rate of outpatient visits (per 100,000 inhabitants)c <1 year 2,130 7 236 1 year 1,034 1 258 2 years 1,034 1 258 3 years 1,034 1 1,034 4 years 1034 1 1,034 5-9 years 262 1 1,050 10-14 years 196 1 787 15-19 years 22 15 89 20-24 years 24 16 109 25-29 years 31 16 142 30-34 years 30 17 136 35-39 years 36 17 165 40-44 years 56 19 254 45-49 years 70 22 135 50-54 years 83 23 159 55-59 years 156 23 298 60-64 years 233 25 446 65-69 years 262 48 174 70-74 years 442 52 294 75-79 years 820 52 546 80-84 years 2,391 65 1,594 85-89 years 2,391 65 1,594 ≥90 years 2,391 65 1,594 a
Based on mortality from Oficina General de Estadística e Informática (OGEI) 2006 [2],divided by the hospital fatality rate assuming that only 46% of deaths occur in hospital [3].
7 b
Based on fatalities reported by studies from Brazil, Chile and Mexico [4, 5] and a personal
communication from División de Planificación Sanitaria, Departamento de Estadísticas e Información de Salud, Ministerio de Salud de Chile, April 2009.
3
To estimate the number of outpatient cases we used the annual hospitalization rate per 100,000 inhabitants and the percentage of pneumonia cases requiring hospitalization (based on Delphi panel from Peru [for pediatric ages] or average from Delphi panels from Chile, Brazil, Mexico and Colombia [for adults]).
8 Supplementary Table 4 Epidemiology of acute otitis media by any cause by age group
Age group Annual outpatients cases (per 100,000 inhabitants)a
Annual
myringotomies (per 100,000 inhabitants)b
Annual cases with sequelae (per 100,000 inhabitants)c <1 year 8943.5 89.4 1207.4 1 year 8136.5 366.2 691.6 2 years 7151.6 321.8 607.9 3 years 7950.7 238.5 318.0 4 years 7523.4 225.7 300.9 5-9 years 4626.9 46.3 69.4 10-14 years 4626.9 46.3 69.4 15-19 years 1133.7 11.3 17.0 20-24 years 969.3 41.2 50.9 25-29 years 908.5 38.6 47.7 30-34 years 908.5 38.6 47.7 35-39 years 908.5 38.6 47.7 40-44 years 908.5 38.6 47.7 45-49 years 841.5 25.2 69.4 50-54 years 841.5 25.2 69.4 55-59 years 841.5 25.2 69.4 60-64 years 846.9 25.4 69.9 65-69 years 709.2 39.0 94.9 70-74 years 709.2 39.0 94.9 75-79 years 709.2 39.0 94.9 80-84 years 709.2 39.0 94.9 85-89 years 709.2 39.0 94.9 ≥90 years 709.2 38.6 94.9 a
9 b
Calculated based on the incidence of outpatient cases and the percentage of cases that would require myringotomy (based on Delphi panel from Peru [for pediatric patients] or average from Delphi panels from Chile, Brazil, Mexico and Colombia [for adults]).
c
Calculated based on the incidence of outpatient cases and the percentage of cases with sequelae (based on Delphi panel from Peru [for pediatric ages] or Delphi panels average from Chile, Brazil, Mexico and Colombia [for adults]).
10 Supplementary Table 5 S. pneumoniae serotype distributiona
Age group Invasive disease (%)
0-2 years 2-5 years 5-10 years >10 years
1 1.7 1.7 3.5 3.5 3 0.6 0.6 0.0 0.0 4 1.1 1.1 0.0 0.0 5 8.1 8.1 6.8 6.8 6A 7.5 7.5 3.4 3.4 6B 8.1 8.1 3.4 3.4 7F 0.0 0.0 0.0 0.0 9V 1.7 1.7 3.5 3.5 14 40.3 40.3 26.5 26.5 18C 1.2 1.2 13.7 13.7 19A 1.7 1.7 5.1 5.1 19F 3.4 3.4 14.5 14.5 23F 2.3 2.3 10.3 10.3 Others 22.3 22.3 9.4 9.4 a Based on SIREVA II [9, 10].
11 Supplementary Table 6 Costs included in the modela
Public scenario costs EsSalud scenario costs Private scenario costs Weighted scenario costs
Children Adults Children Adults Children Adults Children Adults Average cost per acute episode
Pneumonia (hospitalized patients) 278.84 417.94 1,395.61 3,331.54 2,538.11 3,726.26 605.95 926.17
Pneumonia (outpatients) 68.17 112.15 151.63 208.19 293.89 414.28 95.93 146.56
Myringotomy 41.92 45.88 147.60 160.81 300.00 326.91 75.46 82.38
Acute otitis media (outpatients) 41.06 38.43 109.08 99.86 202.81 185.32 62.38 57.73
Meningitis (hospitalized patients) 633.52 627.58 4,033.98 3,827.41 6,079.50 5,870.59 1,545.21 1,492.42 Bacteremia (hospitalized patients) 309.09 446.89 1,938.00 3,176.69 3,400.50 5,037.69 774.28 1,191.77 Average cost per sequelae
Neurologic sequel due to meningitis (non-hypoacusia)
620.38 166.63 1,842.00 494.76 2,657.82 693.88 952.15 254.57
Hypoacusia 40.27 150.74 87.00 336.02 138.61 492.32 54.16 202.97
a
All costs [11-14] were measured in 2009 Nuevos Soles as shown in present table. These costs were converted to 2009 US$ based on the exchange rate of US$1 = 2.78 Nuevos Soles, for the analysis.
13 Supplementary Table 7 Yearly utility decrements
Decrement Source
Short-term disutilities associated with acute pathologiesa
Pneumonia (hospitalized) 0.008 Assumed to be the same as for hospitalized bacteremia [15]
Pneumonia (ambulatory) 0.006 [15]
AOM (ambulatory) 0.005 [16]
AOM with myringotomy 0.005 Assumed the same as for AOM without myringotomy
Pneumococcal meningitis 0.023 [15] Pneumococcal bacteremia 0.008 [15] Long-term disutilities associated with
sequelaeb
Hipoacusia due to AOM 0.090 [17]
Neurologic sequelae due to meningitis
0.400 [18]
Hipoacusia due to meningitis 0.200 [18] a
Applied to current year without discount. b
Applied to current and subsequent years with discount. AOM, acute otitis media.
14 Supplementary Table 8 Parameters included in the sensitivity analysis comparing PHiD-CV and PCV-13 versus no vaccination
Variable Base case Distribution
Type
Range of sensitivity analysis
Pneumonia incidence Age-specific data (see Table 3)
Triangular -/+20% for hospitalizations -/+50% for ambulatory cases
Pneumonia case fatality ratio
Age-specific data (see Table 3)
Triangular -/+20%
AOM incidence Age-specific data (see Table 4)
Triangular -/+20% for myringotomies -/+50% for total cases
AOM etiology Pneumo AOM: 35.9%
NTHi AOM: 32.3% Pneumos covered by PHiD-CV: 76.2%; PCV-13: 89.5%. PCV-7: 69.8% [24, 25]
Triangular -/+20% for Sp cases -/+20% for NTHi cases
Meningitis incidence Age-specific data (See Table 1)
Triangular -/+50%
Meningitis case fatality ratio Age-specific data (See Table 1)
Triangular -/+20%
Meningitis risk of sequelae Age-specific data (See Table 1)
Triangular -/+20%
Bacteremia incidence Age-specific data (See Table 2)
Triangular -/+50%
Bacteremia case fatality ratio
Age-specific data (See Table 2)
15 ID etiology (Sp serotype distribution) Age-specific data (See Table 5) Dirichlet 95% CI ID etiology (Sp in ≥10 years) Age-specific data (See Table 5) Dirichlet -/+20% Effectiveness in reducing hospitalizations for pneumonia 23.4% [19-21] Lognormal 95% CI Effectiveness in reducing ambulatory pneumonia 7.3% [19-21] Lognormal 95% CI
Efficacy in preventing AOM according to type of pathogen 57.6% for SpC; -33% for SpNC; 35.3% for NTHi [22, 23] Lognormal 95% CI
Efficacy in preventing NTHi associated ID
Based on Prymula et al 2006 [22]
Triangular -/+ 20%
Efficacy in preventing PID Based on efficacy by serotype for PCV-7 [26]
Lognormal 95% CI for each serotype Costs of administration and
vaccine wastage
US$1 with 10% wastage Triangular -/+100%
Direct cost of treatment of acute events
Disease-specific data (See Table 6)
Triangular -/+20%
Annual cost of long-term treatment of sequelae
Data specific for each condition
(see Table 6)
Triangular -/+20%
Disutilities associated with AOM (with and without myringotomy)
Data specific for each condition
(see Table 7)
Beta 95% CI
Disutilities associated with acute diseases except AOMa
Data specific for each condition
(see Table 7)
Triangular 95% CI
16 chronic conditions (sequelae)b condition (see Table 7) hearing loss Triangular for Sequelae Death ratio - general
population
Age-specific data [27] Triangular -/+ 20%
Ramp up efficacy
assumptions (all vaccines)
Increase to maximum (published) value with number of doses Triangular for dose 0-2 Lognormal for dose 3 -/+ 20% IC95% a
Per episode. bPer year. AOM, acute otitis media; CI, confidence interval; ID, invasive disease; NTHi, non-typeable Haemophilus influenzae; Sp, Streptococcus pneumoniae; SpC: S. pneumoniae
17 Pneumoccocal Vaccine and Modelling experts collaborating with model development
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